My eosinophil count is elevated; what are the possible causes and recommended next steps?

Elevated Eosinophil Count: Causes and Management

Your elevated eosinophil count requires immediate calculation of the absolute eosinophil count (AEC) to determine severity and guide the diagnostic workup, with allergic disorders being the most common cause if AEC is <1.5 × 10⁹/L, but parasitic infections, eosinophilic esophagitis, and potentially serious hypereosinophilic syndrome must be systematically excluded. 1, 2

Immediate First Steps

Calculate your absolute eosinophil count (AEC) by multiplying the eosinophil percentage by your total white blood cell count. 2

• Mild eosinophilia (0.5-1.5 × 10⁹/L): Most commonly caused by allergic disorders (asthma, allergic rhinitis, atopic dermatitis) or medications in non-endemic areas 1
• Moderate-to-severe eosinophilia (≥1.5 × 10⁹/L): Requires urgent evaluation and should never be attributed to allergy alone 2, 3
• Hypereosinophilia (≥1.5 × 10⁹/L persisting >3 months OR >5.0 × 10⁹/L at any time): Carries significant risk of end-organ damage and mortality 1, 3

Red Flags Requiring Urgent Evaluation

Seek immediate medical attention if you have any of these symptoms with elevated eosinophils: 1

• Cardiac symptoms: Chest pain, shortness of breath, heart failure symptoms, or irregular heartbeat 1
• Pulmonary symptoms: Persistent cough, wheezing, or difficulty breathing 1
• Neurological symptoms: Altered mental status, focal weakness, or peripheral neuropathy 1
• Constitutional symptoms: Fever, unintentional weight loss, or night sweats 1

Most Likely Causes Based on Your Clinical Context

If You Have Travel History to Tropical/Subtropical Regions

Parasitic infections (helminth infections) account for 19-80% of eosinophilia cases in returning travelers and must be excluded first. 1, 4

• Strongyloides stercoralis is particularly dangerous as it can persist lifelong and cause fatal hyperinfection syndrome if you become immunocompromised 1
• Schistosomiasis from fresh water exposure in endemic areas can cause chronic complications including portal hypertension 1
• Critical point: Many helminth-infected patients do NOT have eosinophilia, so normal counts don't exclude infection 1

Required testing if you have travel history: 1

• Three separate concentrated stool specimens for ova and parasites
• Strongyloides serology and culture
• Schistosomiasis serology if fresh water exposure in Africa/tropical regions

If You Have Gastrointestinal Symptoms

Eosinophilic esophagitis should be strongly considered if you experience dysphagia (difficulty swallowing) or food impaction. 5, 1

• Peripheral blood eosinophilia occurs in only 10-50% of adults with eosinophilic esophagitis, so tissue diagnosis via endoscopy is essential 6, 1
• Diagnostic criteria: ≥15 eosinophils per 0.3 mm² on esophageal biopsy after excluding other causes 5
• Requires upper endoscopy with multiple biopsies (minimum 6: 2-3 from proximal and 2-3 from distal esophagus) 1

If You Have Respiratory Symptoms

Asthma and allergic disorders are the predominant cause of mild eosinophilia (500-1500 cells/μL), with chronic cough alone causing eosinophilia in up to 40% of cases. 6

• In children with asthma, 20-100% may have elevated peripheral eosinophil counts, though elevations are typically modest (2-fold) 7
• Eosinophil-targeted therapy reduces severe asthma exacerbations by up to 60% 6, 7

If You Recently Started New Medications

Drug-induced eosinophilia is a common cause and should be considered early in the evaluation. 2, 4

• Document the timing of eosinophilia onset relative to any new medications 2
• Consider discontinuing suspect medications if clinically appropriate

Recommended Diagnostic Workup

For Mild Eosinophilia (0.5-1.5 × 10⁹/L)

1. Detailed history focusing on: 1, 2

   • Travel to endemic regions (timing, fresh water exposure, raw/undercooked meat consumption)
   • New medications started around the time eosinophilia was detected
   • Symptoms of allergic disorders (asthma, rhinitis, eczema)
   • Gastrointestinal symptoms (dysphagia, food impaction, abdominal pain)

2. If travel history to endemic areas: 1

   • Stool microscopy for ova and parasites (3 separate specimens)
   • Strongyloides serology and culture
   • Schistosomiasis serology if relevant exposure

3. If allergic symptoms present: 4

   • Consider allergy testing (skin prick or specific IgE) to identify aeroallergen sensitivity
   • Evaluate for concurrent atopic conditions (50-80% will have multiple allergic manifestations) 7

4. If gastrointestinal symptoms: 1

   • Upper endoscopy with multiple biopsies to evaluate for eosinophilic esophagitis

5. Follow-up: 4

   • Repeat complete blood count with differential to confirm resolution or persistence

For Moderate-to-Severe Eosinophilia (≥1.5 × 10⁹/L)

This level requires more aggressive evaluation and hematology referral if persisting >3 months after infectious causes are excluded. 1, 3

1. Immediate workup to exclude parasitic infections (even without travel history): 1

   • Three separate stool specimens for ova and parasites
   • Strongyloides serology and culture
   • Schistosomiasis serology

2. Assessment for end-organ damage: 1

   • Cardiac: ECG, cardiac troponin, NT-proBNP; echocardiography if troponin elevated or cardiac symptoms present
   • Pulmonary: Chest X-ray, pulmonary function tests if respiratory symptoms
   • Neurologic: Electromyography if sensory or motor deficits present
   • Gastrointestinal: Endoscopy with biopsies if GI symptoms

3. Hematologic evaluation: 3

   • Peripheral blood smear review
   • Bone marrow biopsy with cytogenetics and molecular testing to exclude myeloid/lymphoid neoplasms with PDGFRA, PDGFRB, or FGFR1 rearrangements
   • Flow cytometry to detect aberrant T-cell clones

Treatment Considerations

Treatment depends entirely on identifying the underlying cause—do NOT start corticosteroids before excluding parasitic infections, as this can cause fatal complications with certain parasites like Strongyloides. 1, 3

If Parasitic Infection Confirmed

• Strongyloidiasis: Ivermectin 200 μg/kg daily for 2 days 1
• Schistosomiasis: Praziquantel 40 mg/kg single dose, repeated at 6-8 weeks 1
• Critical warning for Loa loa: Do NOT use diethylcarbamazine if microfilariae seen on blood film—can cause fatal encephalopathy; use corticosteroids with albendazole first 1

If Eosinophilic Esophagitis Confirmed

• First-line: Topical swallowed corticosteroids (fluticasone or budesonide) decrease blood eosinophil counts in 88% of patients 6, 1
• Maintenance therapy is mandatory after achieving remission, as relapse rates are high after steroid withdrawal 1
• Endoscopic dilation for fibrostenotic disease, combined with anti-inflammatory therapy 1

If Hypereosinophilic Syndrome or EGPA

• Corticosteroids are first-line for idiopathic HES and EGPA 8, 3
• Exception: If PDGFRA or PDGFRB rearrangements detected, imatinib is the treatment of choice with exquisite responsiveness 3
• Mepolizumab (IL-5 antagonist) recently FDA-approved for idiopathic HES 3

Critical Pitfalls to Avoid

• Do NOT assume normal eosinophil counts exclude parasitic infection—many infected patients have normal counts 1
• Do NOT rely solely on peripheral eosinophil counts to assess tissue eosinophilia in conditions like eosinophilic esophagitis—tissue biopsy is the gold standard 6, 1
• Do NOT wait for symptoms to develop before investigating persistent moderate-to-severe eosinophilia—end-organ damage can be subclinical initially 1
• Do NOT start corticosteroids before excluding parasitic infections, particularly Strongyloides, which can cause fatal hyperinfection syndrome 1, 3
• Do NOT attribute hypereosinophilia (≥1.5 × 10⁹/L) to allergy alone—this should always prompt further workup 2

When to Refer to Specialist

• Hematology referral: If eosinophilia ≥1.5 × 10⁹/L persists >3 months after infectious causes excluded or treated 1, 3
• Gastroenterology referral: If dysphagia, food impaction, or other GI symptoms present 1
• Infectious disease referral: If travel history to endemic areas or suspected parasitic infection 1
• Allergy/Immunology referral: If multiple atopic conditions or severe asthma present 7